3Center of Studies in Diabetes, Research Center in Public Health, National Institute of Public Health, Mexican Institute of Social Security, American British Cowdray Medical Center, Mexico City, Mexico

The role of obesity for the metabolic syndrome definition is controversial (1,2) even though obesity is strongly related to insulin resistance (fasting insulin levels) (3), chronic inflammation (high-sensitivity C-reactive protein [hsCRP] levels) (4), and coronary heart disease (CHD) (5). Obesity is considered an essential criterion by the International Diabetes Federation definition (1). However, the National Cholesterol Education Program-Adult Treatment Panel III definition accepts any three of five criteria (2). If obesity were essential, significant insulin and hsCRP levels and CHD risk would not be present in lean subjects. We examined this hypothesis in populations from Mexico City and Spain because of their distinct risk factor profile (more cases of type 2 diabetes, low HDL cholesterol, and hypertriglyceridemia in Mexico City vs. more cases of hypertension and hypercholesterolemia in Spain) (6).

RESEARCH DESIGN AND METHODS—

The Mexico City Diabetes Study (7,8) from Mexico City and the Spanish Insulin Resistance Study (6) and Segovia Study (9) from Spain were designed as population-based studies. The two studies from Spain were fused in a single dataset because protocols and one of the principal investigators (M.S.-R.) were the same for both studies.

Nondiabetic subjects were considered eligible for analysis (in Spain, n = 1,311; in Mexico City, n = 1,918) because of the absence of a reliable surrogate of insulin resistance for diabetic subjects. Framingham risk equations were used to estimate CHD risk (10) for two reasons: 1) absence of prospective data in Spain and 2) small number of both cardiovascular events and lean subjects with multiple metabolic disorders in Mexico City. Specific insulin was measured by radioimmunoassay in Mexico City (interassay coefficient of variation [CV] 3–7%) (Linco Research, St. Louis, MO) (7) and by immunoassay in Spain (9.1–11.4%) (Linco Research); hsCRP was measured by immunoassay in Mexico City (8.9%) (Calbiochem, Darmstadt, Germany) (8) and in Spain (3.3%) (Beckman Coulter, Fullerton, CA).

We used one-way ANCOVA to analyze insulin and hsCRP levels and Framingham risk estimates to account for the effect of age and sex. We performed analyses on the log-transformed values of insulin and hsCRP levels and on the logit transformation of Framingham risk estimates to correct for skewness and kurtosis. These variables were then back-transformed to their natural units for presentation.

RESULTS—

In Spain and Mexico City, 26.3 and 55.2% of subjects had three or more metabolic disorders, respectively. Normal waist circumference was present in 5.2% of Spanish subjects with three or more metabolic disorders and in 4.8% of Mexican counterparts.

Among subjects with one or more metabolic disorders, elevated waist circumference was directly related to the number of disorders (Table 1). Insulin and hsCRP levels and CHD risk estimates were not increased in subjects with elevated waist circumference after adjusting for number of metabolic components, except for insulin levels in Mexico City.

CONCLUSIONS—

In the U.S. population, 4.6% of men and 6.2% of women with normal weight have three or more metabolic disorders (11). Normal-weight individuals may have insulin resistance. Insulin-resistant, normal-weight individuals have more cardiovascular disease risk factors (12,13), greater CHD and diabetes risks (14–16), and more total and intra-abdominal fat than insulin-sensitive, normal-weight individuals (14). Similarly, absence of central obesity, as assessed by waist circumference, cannot rule out the presence of multiple metabolic disorders (17). Our results indicate that significant insulin and hsCRP levels and CHD risk estimates may be present in subjects with metabolic disorders other than obesity.

There is much support in the literature for the concept that waist circumference is not an independent predictor of CVD and that risk increases with number of components (18,19). The component most strongly associated with insulin resistance is obesity, but clustering of metabolic disorders greatly exceeds chance association in both obese and lean individuals (3). The cross-sectional design of this study limits our ability to reach conclusions. Nevertheless, our results suggest that the metabolic syndrome is not found exclusively in obese individuals.

Footnotes

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

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